RESUMEN
BACKGROUND: The C-C chemokine receptor Type 5 (CCR5) is a key receptor for human immunodeficiency virus type 1 (HIV-1) entry into T-cells and a variant allele, CCR5 delta-32, is associated with decreased viral replication and disease progression. Active HIV-1 replication is highly associated with accelerated rates of hepatic fibrosis. We postulated that CCR5 plays a role in the development of hepatic fibrosis and evaluated the longitudinal effect of natural or drug-induced CCR5 mutation and blockade on biomarkers of liver fibrosis in HIV-1 patients. METHODS: To accomplish this goal, we examined 2 distinct cohorts. First, we evaluated fibrosis markers in the Multicenter Hemophilia Cohort Studies (MHCS), which included subjects with HIV and hepatitis C virus (HCV) coinfection with the CCR5 delta-32 allele. We also evaluated an HIV-1 infected cohort that was treated with a dual CCR5/CCR2 antagonist, cenicriviroc. The enhanced liver fibrosis (ELF) index was validated against liver histology obtained from HCV/HIV and HCV patients and demonstrated strong correlation with fibrosis stage. RESULTS: In both the MHCS patients and patients treated with cenicriviroc, CCR5 mutation or blockade was associated with a significant decrease in the ELF index. Among the patients with the delta-32 allele, the ELF index rate significantly decreased in sequential samples as compared to CCR5 wild-type patients (P = .043). This was not observed in control subjects treated with efavirenz nor with a lower dose of 100 mg cenicriviroc. CONCLUSION: These findings suggest that hepatic fibrosis in HIV-1 infected patients can be modulated by the mutation of CCR5 and/or use of CCR5/CCR2 blockade agents. CLINICAL TRIALS REGISTRATION: NCT01338883.
Asunto(s)
Infecciones por VIH/complicaciones , Hepatitis C/complicaciones , Imidazoles/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/inmunología , Receptores CCR5/genética , Adolescente , Adulto , Anciano , Alelos , Biomarcadores/análisis , Antagonistas de los Receptores CCR5/uso terapéutico , Niño , Preescolar , Estudios de Cohortes , Coinfección/complicaciones , Coinfección/virología , Método Doble Ciego , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Hepacivirus , Humanos , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Mutación , Estudios Observacionales como Asunto , Sulfóxidos , Adulto JovenRESUMEN
Hepatitis D virus (HDV) infection may accompany acute or chronic hepatitis B virus infection. While HDV infection in the United States is thought to be uncommon, there are limited data regarding frequency of testing, and prevalence of HDV antibody and HDV RNA. We evaluated the use of HDV antibody testing using electronic medical record (EMR) data. Among 1007 HBsAg positive patients, only 121 had been tested for HDV antibody. Testing was performed primarily by gastroenterologists/hepatologists and limited testing was performed in identifiable high risk groups including those with HBV/HIV coinfection. Overall, HDV antibody was detected in 3.3% (95% C.I.â¯=â¯0.9%-8.2%) An HDV RNA assay was developed and validated and 138 HBV or HBV/HIV coinfected patients were tested. The prevalence of HDV among the HBV/HIV coinfected subjects was 2.2% (95% C.I.â¯=â¯0-5.3%). In a U.S. Midwestern population of HBV infected patients, HDV testing is under-employed. Overall prevalence exceeds 2% whether testing by antibody or HDV RNA and more comprehensive HDV surveillance may be indicated.
Asunto(s)
Coinfección/virología , Anticuerpos Antihepatitis/sangre , Hepatitis D/diagnóstico , Virus de la Hepatitis Delta/aislamiento & purificación , Técnicas de Diagnóstico Molecular/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Coinfección/epidemiología , Femenino , Infecciones por VIH/epidemiología , Hepatitis B/epidemiología , Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis B Crónica/epidemiología , Hepatitis D/epidemiología , Virus de la Hepatitis Delta/genética , Humanos , Masculino , Persona de Mediana Edad , Medio Oeste de Estados Unidos/epidemiología , Prevalencia , Reacción en Cadena en Tiempo Real de la Polimerasa , Estados Unidos/epidemiología , Adulto JovenRESUMEN
AIM: To study the intrahepatic expression of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in chronic hepatitis B patients with and without hepatocellular carcinoma. METHODS: A total of 33 chronic hepatitis B patients (mean age of 40.3 ± 2.5 years), comprising of 14 HBeAg positive and 19 HBeAg negative patients; and 13 patients with hepatitis B virus related hepatocellular carcinoma (mean age of 49.6 ± 4.7 years), were included in our study. Immunohistochemical staining for HBcAg and HBsAg was done using standard streptavidin-biotin-immunoperoxidase technique on paraffin-embedded liver biopsies. The HBcAg and HBsAg staining distributions and patterns were described according to a modified classification system. RESULTS: Compared to the HBeAg negative patients, the HBeAg positive patients were younger, had higher mean HBV DNA and alanine transaminases levels. All the HBeAg positive patients had intrahepatic HBcAg staining; predominantly with "diffuse" distribution (79%) and "mixed cytoplasmic/nuclear" pattern (79%). In comparison, only 5% of the HBeAg-negative patients had intrahepatic HBcAg staining. However, the intrahepatic HBsAg staining has wider distribution among the HBeAg negative patients, namely; majority of the HBeAg negative cases had "patchy" HBsAg distribution compared to "rare" distribution among the HBeAg positive cases. All but one patient with HCC were HBeAg negative with either undetectable HBV DNA or very low level of viremia. Intrahepatic HBcAg and HBsAg were seen in 13 (100%) and 10 (77%) of the HCC patients respectively. Interestingly, among the 9 HCC patients on anti-viral therapy with suppressed HBV DNA, HBcAg and HBsAg were detected in tumor tissues but not the adjacent liver in 4 (44%) and 1 (11%) patient respectively. CONCLUSION: Isolated intrahepatic HBcAg and HBsAg can be present in tumors of patients with suppressed HBV DNA on antiviral therapy; that may predispose them to cancer development.
Asunto(s)
Carcinoma Hepatocelular/virología , Antígenos del Núcleo de la Hepatitis B/análisis , Antígenos de Superficie de la Hepatitis B/análisis , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/virología , Neoplasias Hepáticas/virología , Hígado/virología , Adulto , Anciano , Antivirales/uso terapéutico , Biopsia , Carcinoma Hepatocelular/diagnóstico , ADN Viral/genética , Femenino , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Inmunohistoquímica , Hígado/efectos de los fármacos , Hígado/patología , Neoplasias Hepáticas/diagnóstico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Carga ViralRESUMEN
BACKGROUND: Patients with inflammatory bowel disease have higher proportions of immunoglobulin G (IgG) antibodies lacking N-galactose, also called agalactosyl IgG, in their serum. Such agalactosyl IgGs have been associated with disease activity and the immunogenicity of biologics. The aim was to describe the relationship between circulating levels of a subset of agalactosyl IgGs (anti-α-Gal) and Crohn's disease (CD) phenotypes. METHODS: Prospectively collected serum samples of a well-characterized cohort of patients with inflammatory bowel disease and controls were used. Serum anti-α-Gal levels were measured by a high-affinity enzyme-linked immunosorbent assay and referenced to a standard control. RESULTS: Serum samples from 167 subjects were tested; 62 with CD, 76 with ulcerative colitis, and 29 controls. Agalactosyl anti-α-Gal levels were significantly higher in active CD than in active ulcerative colitis (P = 0.0043) or healthy controls (P < 0.0001). Among patients with CD, agalactosyl anti-α-Gal levels were significantly higher in those with a history of arthritis, than those without (P = 0.0002), but lower in those taking immunomodulators (P = 0.03). There was no correlation between agalactosyl anti-α-Gal levels and indices of Crohn's severity, including C-reactive protein levels or Harvey-Bradshaw index. Patients who were primary or secondary nonresponders to infliximab had similar agalactosyl anti-α-Gal levels to clinical responders. CONCLUSIONS: Patients with CD have greater amounts of agalactosylated anti-α-Gal antibodies in their serum, particularly in those with associated joint disease. This increase seems to be independent of indices of disease activity, but is influenced by immunomodulator use.